Background: Extracorporeal photochemotherapy (ECP) using UVA irradiation of enriched leukocytes in the presence of methoxsalen as a photoactivatable substrate has been employed for the treatment of several immunologically mediated disorders. Objective: Our purpose was to determine the efficacy and safety of long-term ECP in the treatment of severe atopic dermatitis. Methods: Fourteen patients with severe recalcitrant atopic dermatitis were treated with ECP in an open clinical trial at 2-week intervals. Disease activity was scored before each ECP cycle by means of a standardized protocol. Results: A complete clinical remission was achieved in 4 patients (29%). Five patients (36%) experienced a substantial response with reduction of skin inflammation by at least 75%, whereas in one patient (7%) disease activity was reduced by more than 50%. Four patients were withdrawn from the study for unresponsiveness. No clinical signs of immunosuppression or other severe adverse events became evident. Conclusion: Long-term ECP may have significant beneficial effects on the course of atopic dermatitis and should therefore be considered as a treatment modality for patients suffering from severe and otherwise refractory atopic skin disease. (J Am Acad Dermatol 1999;40:577-82.)